The horse lentivirus, equine infectious anemia virus (EIAV), is a virus closely related to the human AIDS virus, HIV. We wish to use this virus as an animal model for HIV. However, to do this, more of the basic biology of EIAV needs to be understood. Three projects are currently ongoing on the biology of EIAV. First is the characterization of infection and growth of EIAV in its target cell, the macrophage. In collaboration with Susan Carpenter, studies are underway characterizing regions within the LTR, the viral promoter, which are important for transcriptional regulation of the virus in macrophages. In concurrent studies, attempts are being made to identify proteins that are synthesized in macrophages that interact with LTR sequences. Second, reconstruction of a molecular clone of EIAV is in progress. The molecular clone was derived by Dr. Carpenter while she was at Rocky Mountain Labs. This clone is not infectious, at least in part because of a stop codon in the envelope gene. Using site directed mutagenesis, we are replacing the stop codon and will determine if the molecular clone is now infectious. In parallel with this work, stop codons are separately being introduced into the three small open reading frames found in EIAV. These reading frames are believed to produce peptides that have similar functions to the small regulatory proteins found in HIV. Functional analysis of these mutations will follow. In a third project, we are attempting to isolate a new field isolate of EIAV. The only two independently derived molecular clones currently characterized have been found to be quite similar at both the nucleotide and amino acid levels. To begin to understand the heterogeneity of EIAV, a third independent isolate will be analyzed. Knowledge of the sequence heterogeneity within the horse population at large has important implications for vaccine development.